This proposal describes the development of a microfabricated conductimetric glucose biosensor of a size suitable for subcutaneous implantation. Management of Type I diabetes would be greatly enhanced by the availability of such a sensor, which might be used in acute care situations such as hospitalization of a diabetic patient at risk for hypoglycemia, or in developing a insulin administration regimen. An implantable sensor which could operate reliably for a period of six months would, when linked to an insulin infusion system, make feasible an artificial pancreas. There is evidence that such a system would lead to tighter control of blood glucose and reduce the long term complications resulting from the disease. The proposed sensor is fundamentally different from existing sensors, and is based on a measurement of the electrical conductivity of a "glucose- sensitive" hydrogel. The enzyme glucose oxidase, immobilized within a polymer gel, catalyzes the formation of gluconic acid from glucose. This causes swelling of the gel and a concomitant change in the electrical conductivity of the gel. Miniature electrodes, patterned on a silicon or glass "chip" are used to measure the conductivity of the gel. One potential advantage of the proposed conductimetric sensor is that there should be little, if any oxidation or reduction of electroactive species at the electrodes. The response should therefore not be affected by substances such as acetaminophen which can interfere with some current sensors. Planar microfabrication technology simplifies sensor construction and can produce large numbers of identical sensors of the required size, on the order of 0.5 mm for subcutaneous implantation. The experimental plan detailed herein will lead to the development and in vivo evaluation of the sensor. Specific aims include the i) continued development of lithographic methods for preparing "glucose-responsive" hydrogels to insure thickness and compostional uniformity; (ii) modelling of diffusion-reaction in the glucose-sensitive hydrogel to aid in the optimization of the gel composition; (iii) development of permselective polyurethane outer membranes to extend the operating range of the sensor; (iv) in vitro testing to evaluate and optimize sensor sensitivity, range, selectivity and response time, and (v) acute subcutaneous testing in a rat animal model to identify the factors impacting sensor performance in a biological environment.